A systematic clinical neuroscience protocol is described for the use to examine the trigemino-cardiac reflex (TCR) response in humans. Target neurosurgical conditions are operations that require manipulations around the peripheral and central part of the trigeminal nerve and its branches, e.g. the cerebellopontine angle or the sellar region. To assess the hemodynamic and cardiac responses of patients after TCR initiation, anesthetic monitoring has been applied. The TCR is defined as a drop of more than 20% of the heart rate and the mean arterial blood pressure compared with the baseline values before the stimulus and coinciding with the surgical manipulation at or around any branches of the trigeminal nerve. By help of illustrative cases, we present for the first time preliminary results regarding the differentiation of the TCR in a central and a peripheral induction during transsphenoidal surgery of pituitary adenomas. Based on these results, we can conclude that we have developed a battery of preoperative examination procedures based on event-related diagnostics that was useful to differentiate different subgroups of TCR during transsphenoidal surgery. The presented protocol can be performed directly pre-, intra- and postoperatively and applied for assessment of TCR even in patients with known risk factors.